Aspergillus fumigatus is a ubiqutous spore-bearing fungus that causes multiple diseases in humans. These include allergic pulmonary asthma, aspergillomas, and invasive disease of hosts usually with predisposing underlying conditions. For example, in the United States in 1996, there were an estimated 10,190 aspergillosis-related hospitalizations; these resulted in 1970 deaths, 176,300 hospital days, and $633.1 million in costs. The average hospitalization lasted 17.3 days at a cost of about $62,000. Although aspergillosis-related hospitalizations account for a small percentage of hospitalizations in the United States, patients hospitalized with the condition have lengthy hospital stays and high mortality rates. The high mortality rates (in some instances over 90%) are due in part to the lack of rapid and sensitive diagnostics tests (all too often the diagnosis is done post mortem) as well as the lack of effective anti-fungals. Our long-term goal is to develop a safe and effective vaccine against A. fumigatus. In this SBIR Phase I proposal, we will use a novel, proprietary recombinant antigen delivery system and test a number of A. fumigatus proteins as vaccine candidates. We will accomplish this in two specific aims: Specific Aim One: Engineer yeast cells to express each of seven A. fumigatus putative antigens using recombinant DNA technology. Specific Aim Two: Test the in vivo efficacy of each vaccine formulation to protect vaccinated animals against a challenge of A. fumigatus. This work will be a prelude to work in Phase II that will include detailed testing for in vivo efficacy and safety of each vaccine candidate. Ultimately, the Phase I, subsequent Phase II and III research will lead to the development of a vaccine against A. fumigatus.